Target achieved: smooth and young skin for longer

www.lipotec.com

An alternative mechanism against expression wrinkles

Inhibits muscular contraction through Ca2+

leuphasyl® and argireline®

peptides, a revolutionary tandem

DescriptionPentapeptide that mimics the natural path of enkephalins, acting on expression wrinkles formation in a new way. This alternative mechanism offers compatibility with other anti-wrinkle peptides, providing an additive and synergistic effect.

AppearanceTranslucent solution containing ingredient.

INCIWater (Aqua), Glycerin, Pentapeptide-18, Caprylyl Glycol.Preservative free.

Propertiesleuphasyl® peptide reduces the depth of wrinkles caused by the contraction of muscles of facial expression, decreasing neuron excitability and modulating acetylcholine secretion. The diminution of wrinkles increases with argireline® peptide, due to their additive effects.

Applicationsleuphasyl® peptide can be incorporated in cosmetic formulations where removal of wrinkles, especially in the forehead and around the eyes, is desired.

ScienceExpression wrinkles are a particular type linked to repeated muscular contraction and they usually appear as soon as the age of 30. Muscles are contracted when they receive acetylcholine released from a vesicle in the neuronal exocytosis. In order to fuse a vesicle with the cellular membrane, two events are required: the SNARE complex formation and the entry of calcium ions into the neuron.leuphasyl® peptide is a modified enkephalin that couples to the enkephalin receptor, outside of nerve cells. This association releases G protein subunits (α,ß,Y), which close calcium channels avoiding vesicle fusion and consequently inhibiting acetylcholine release across the synapse. This process maintains the neuron in its resting state, attenuating muscle contraction and preventing the formation of lines and wrinkles.

Dosage 3-10%

SolubilityWater soluble.

anti-wrinkles

0.05% active

In neuronal exocytosis acetylcholine is released, which is necessary for muscle contraction. This neurotrasnmitter drives from the fusion of the fixed vesicle in the cellular membrane throught the SNARE complex, produced in the presence of calcium ions. Muscular contraction is attenuated twice by blocking ions entrance, with leuphasyl® peptide, and modulation the formation of the SNARE complex, with argireline® peptide.

In vitro synergistic effect in the inhibition of neurotransmitters releaseThe independent mechanisms of leuphasyl® peptide and argireline® peptide show together a higher inhibitory potential in glutamate release, because of their complementary effects.

Additive effect in wrinkles reductionThe combination of both peptides shows a reduction in the depth of wrinkles of 25%, with maximum values up to 47%.

COMPARATIVE TEST TO DETERMINE THE ANTI-WRINKLE EFFECT Three tests were performed, using a placebo cream, with several solutions of the peptides (containing 0.05% of active ingredient), applying the cream twice a day around the eyes, for 28 days.

Efficacy of anti-wrinkle peptides was evaluated by taking silicon imprints of thewrinkles around the eyes. Silicon imprints were measured by confocal profilometry.

MODULATION OF GLUTAMATE RELEASE IN A NEURON CELL CULTURE The glutamate is the most abundant neurotransmitter in the nervous system and its release is used as a validated assay to determine the release of acetylcholine. The release of glutamate in a primary cell culture of neurons is measured in order to compare the in vitro activities of the anti-expression wrinkle ingredients leuphasyl® peptide and argireline® peptide.

In vitro action mechanism

In vitro efficacy

In vivo efficacy

28 days0 days

leuphasyl®peptide solution 5%

leuphasyl® peptide solution 5% +argireline® peptide solution 5%

Actives Volunteers Age0

-5

-10

-15

-20

-25Wri

nkl

e re

du

ctio

n (%

)

leuphasyl® peptide + argireline® peptide

leuphasyl®

peptide

-11.6%

-24.6%

leuphasyl® peptide +argireline® peptide

Muscle contraction

Enkephalin receptors

K+

Ca2+ Ca2+ Ca2+

K+ K+

Giproteins

Giproteins

Giproteins

Enkephalin receptors

Enkephalin receptors

leuphasyl® peptide

Glu

tam

ate

rele

ase

(%) In

hib

ition

glu

tamate

release (%)

100

80

60

40

20

0

0

20

40

60

80

100

argireline®

peptide1mM

argireline®

peptide2mM

Control leuphasyl®peptide1mM

leuphasyl®peptide2mM

argireline®

peptide 1mM +leuphasyl®

peptide 1mM

5% leuphasyl® peptide solution

5% leuphasyl® peptide solution +5% argireline® peptide solution

14

15

39-64 years old

39-63 years old

20%

11%

40%

32%19%

Isaac Peral 17 Pol. Industrial Camí Ral - 08850 Gavà (Barcelona) Spain-Tel +34 93 638 80 00 / Fax +34 93 638 93 93 - commercial@lipotec.com

The trademarks referenced in this brochure are owned by The Lubrizol Corporation. While the claims and supporting data provided in this publication are believed to be reliable and they are presented free and for guidance only, there are no warranties of any kind. All express and implied warranties are disclaimed. The recipient is solely responsible for ensuring that products marketed to consumers comply with all relevant laws and regulation. LIPOTEC is the exclusive holder of the both industrial and intellectual property rights identified herein. Recipient of this publication agrees to indemnify and hold harmless each entity of the LIPOTEC organization for any and all regulatory action arising from recipient’s use of any claims or information in this publication, including, but not limited to, use in advertising and finished product label claims, and not present this publication as evidence of finished product claim substantiation to any regulatory authority.

Ed. 13G

© 2013 The Lubrizol Corporation.All Rights Reserved.